Automated Analyzer

ABSTRACT

An automated analyzer for analyzing patient samples. The analyzer includes a plurality of cuvettes, which allow the samples to be mixed with various reagents. The analyzer includes one or more detectors, including a detector adapted to detect luminescence of the reaction mixture in the cuvettes. The analyzer allows for various diagnostic assays to be performed on a single system, and provides for high-sensitivity analysis at faster speeds.

RELATED APPLICATIONS

This application is a Continuation of U.S. patent application Ser. No.11/261,952 filed Oct. 27, 2005, which claims priority to U.S. patentapplication Ser. No. 10/862,507 filed Jun. 7, 2004 (issued as U.S. Pat.No. 7,381,370 on Jul. 3, 2008), which claims priority to U.S.Provisional Patent Application No. 60/488,336 filed Jul. 18, 2004.

FIELD OF THE INVENTION

The present invention relates to an apparatus for automaticallyprocessing a patient's biological fluid samples such as urine, bloodserum, plasma, cerebrospinal fluid and the like. In particular, thepresent invention provides an automated system having multiple detectorsfor analysis of the samples according to one or more of a number ofassay protocols.

BACKGROUND OF THE INVENTION

Various types of tests related to patient diagnosis and therapy can beperformed by analysis of a sample taken from a patient's infections,bodily fluids or abscesses. These assays typically involve automatedanalyzers onto which vials containing patient samples have been loaded.The analyzer extracts the samples from the vials and combines thesamples with various reagents in special reaction cuvettes or tubes.Frequently, the samples are incubated or otherwise processed beforebeing analyzed. Analytical measurements are often performed using a beamof interrogating radiation interacting with the sample-reagentcombination, for example turbidimetric, fluorometric, absorptionreadings or the like. The measurements allow determination of end-pointor rate values from which an amount of analyte may be determined usingwell-known calibration techniques.

Although various known clinical analyzers for chemical, immunochemicaland biological testing of samples are available, analytical clinicaltechnology is challenged by increasing needs for improved levels ofanalysis. The improvement of analytical sensitivity continues to be achallenge. Furthermore, due to increasing pressures on clinicallaboratories to reduce cost-per-reportable result, there continues to bea need for improvements in the overall cost performance of automatedclinical analyzers. Often a sample to be analyzed must be split into anumber of sample aliquots in order to be processed by several differentanalytical techniques using different analyzers. Sample analysiscontinuously needs to be more effective in terms of increasing assaythroughput and increasing speed, as well as providing an increasednumber of advanced analytical options so as to enhance a laboratory'sefficiency in evaluating patient samples. In particular, the results ofa first battery of assays on a sample often dictate that a secondbattery of different assays be performed in order to complete or confirma diagnosis, called reflux or add-on testing. In such an instance, thesecond battery of assays is often performed with a more sophisticatedanalytical technique than the first battery so that sample must beshuffled between different analytical laboratories. In addition toincreased inefficiency, extra sample handlings increase the possibilityof errors.

Automated clinical analyzers are typically controlled by softwareexecuted by a computer using software programs written in a machinelanguage like on the Dimension® clinical chemistry analyzer sold by DadeBehring Inc, of Deerfield, Ill., and widely used by those skilled in theart of computer-based electromechanical control programming. Such acomputer executes application software programs for performing assaysconducted by the analyzer but it is also required to be programmed tocontrol and track, among other items:

-   -   various analytical devices for performing 100+ different assays        on different samples like blood, serum, urine and the like;    -   re-testing and add-on testing of samples when required by prior        results;    -   the patient's identity, the tests to be performed, if a sample        aliquot is to be retained within the analyzer;    -   calibration and quality control procedures;    -   an incoming and outgoing sample tube transport system;    -   inventory and accessibility of sample aliquots within an        environmental chamber;    -   washing and cleaning reusable cuvettes;    -   reagent and assay chemical solution consumption along with time,        and date of consumption of all reagents consumed out of each        reagent container and assay chemical solutions consumed out of        each vial container on a per reagent container, per calibration        vial container, per Quality Control container, per assay, and        per calibration basis, for specifically defined time periods;        and,    -   scheduling at least 1000 assays per hour.

From the above descriptions of the complex multiple operations conductedwithin a clinical analyzer, it is apparent that increasing the abilityof a single analyzer to perform analytical tests using a relativelylarge number of different assay formats in a “user-friendly” mannerpresents much greater challenges than are encountered when an analyzerconducts, for example, only two different assay formats. However, withinthe clinical diagnostic field there is a continuing need for new andaccurate analytical techniques that can be adapted for a wide spectrumof different analytes or be used in specific cases where other methodsmay not be readily adaptable. Convenient, reliable and non-hazardousmeans for detecting the presence of low concentrations of materials inliquids is desired. In clinical chemistry these materials may be presentin body fluids in concentrations below 10.sup.-12 molar. The difficultyof detecting low concentrations of these materials is enhanced by therelatively small sample sizes that can be utilized. In developing anassay there are many considerations. One consideration is the signalresponse to changes in the concentration of analyte. A secondconsideration is the ease with which the protocol for the assay may becarried out. A third consideration is the variation in interference fromsample to sample. Ease of preparation and purification of the reagents,availability of equipment, ease of automation and interaction withmaterial of interest are some of the additional considerations indeveloping a useful assay.

Luminescent compounds, such as fluorescent compounds andchemiluminescent compounds, find wide application in the assay fieldbecause of their ability to emit light. For this reason, luminescershave been utilized as labels in assays such as nucleic acid assays andimmunoassays. For example, a member of a specific binding pair isconjugated to a luminescer and various protocols are employed. Theluminescer conjugate can be partitioned between a solid phase and aliquid phase in relation to the amount of analyte in a sample suspectedof containing the analyte. By measuring the luminescence of either ofthe phases, one can relate the level of luminescence observed to aconcentration of the analyte in the sample.

Particles, such as latex beads and liposomes, have also been utilized inassays. For example, in homogeneous assays an enzyme may be entrapped inthe aqueous phase of a liposome labeled with an antibody or antigen. Theliposomes are caused to release the enzyme in the presence of a sampleand complement. Antibody or antigen-labeled liposomes, having watersoluble fluorescent or non-fluorescent dyes encapsulated within anaqueous phase vesicle or lipid soluble dyes dissolved in the lipidbilayer of a lipid, have also been utilized to assay for analytescapable of entering into an immunochemical reaction with the surfacebound antibody or antigen. Detergents have been used to release the dyesfrom the aqueous phase of the liposomes. Chemiluminescent labels offerexceptional sensitivity in ligand binding assays, but one or morechemical activation steps are usually needed. Fluorescent labels do nothave this deficiency but are less sensitive.

U.S. Pat. Nos. 5,340,716 and 5,709,994 discloses a method fordetermining an analyte in a highly sensitive assay format known as aLuminescent Oxygen Channeled Immunoassay (LOCI) using a label reagentcomprising a first specific binding pair member associated with aparticle having a photosensitizer capable upon activation of generatingsinglet oxygen and a chemiluminescent compound capable of beingactivated by singlet oxygen such that upon activation of thephotosensitizer, singlet oxygen is generated and activates thechemiluminescent compound, wherein the first specific binding pairmember is capable of binding to the analyte or to a second specificbinding pair member to form a complex related to the presence of theanalyte; the photosensitizer is activated and the amount of luminescencegenerated by the chemiluminescent compound is detected and related tothe amount of analyte in the sample.

U.S. Pat. No. 5,807,675 discloses a method for determining an analyte ina less sensitive assay format known as a Fluorescent Oxygen ChanneledImmunoassay (FOCI) using a photosensitizer capable in its excited stateof generating singlet oxygen, wherein the photosensitizer is associatedwith a first specific binding pair member in combination with aphotoactive indicator precursor capable of forming a photoactiveindicator upon reaction with singlet oxygen, wherein the photoactiveindicator precursor is associated with a second specific binding pairmember. The combination is irradiated with light to excite thephotosensitizer, and in a final step, the fluorescence is measured andrelated to the amount of the analyte in the sample.

Homogeneous immunoassays in which it is unnecessary to separate thebound and unbound label have previously been described for smallmolecules. These assays include SYVA's FRAT assay, EMIT® assay, enzymechanneling immunoassay, and fluorescence energy transfer immunoassay(FETI); enzyme inhibitor immunoassays (Hoffman LaRoche and AbbottLaboratories): fluorescence polarization immunoassay (Dandlicker), amongothers. All of these methods have limited sensitivity, and only a fewincluding FETI and enzyme channeling, are suitable for largemultiepitopic analytes. Heterogenous immunoassays in which a separationstep is required are generally useful for both small and largemolecules. Various labels have been used including enzymes (ELISA),fluorescent labels (FIA), radiolabels (RIA), chemiluminescent labels(CLA), etc. Clinical analyzers in which such homogeneous andheterogenous immunoassays are commercially available and these aregenerally quite complex. See for example, U.S. Pat. Nos. 6,074,615 and5,717,148 and 5,985,672 and 5,635,364. From a consideration of patentssuch as these, it becomes obvious that many challenges are created whenclinical analyzers having automated immunoassay systems are to beenhanced in capability with the additional automated ability to performsensitive Luminescent Oxygen Channeled Immunoassays.

SUMMARY OF THE INVENTION

The analyzer of the present invention allows for various diagnosticassays to be performed on a single system, and provides for highersensitivity as well as faster processing speeds. According to one aspectof the invention, an automated includes a plurality of cuvettes, eachadapted to contain a reaction mixture including a sample and one or morereagents. The analyzer includes a LOCI reader adapted to detectluminescence of a reaction mixture in one or more of the cuvettes. Oneor more other detectors may also be included and are adapted to performother analysis of a reaction mixture in one or more of the cuvettes orin a liquid flow-through cell. A cuvette transport mechanism is adaptedto move the cuvettes to the detectors. The analyzer also includes acontrol mechanism adapted to control the detectors and the cuvettetransport mechanism. Further aspects of the invention will be evidentbased on the claims that follow the detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood from the following detaileddescription thereof taken in connection with the accompanying drawingswhich form a part of this application and in which:

FIG. 1 is a schematic plan view of an automated analyzer illustrative ofthe present invention;

FIG. 2 is an enlarged schematic plan view of a portion of the analyzerof FIG. 1;

FIG. 3 is a perspective view of a reagent container useful in theanalyzer of FIG. 1;

FIG. 3A is a perspective view of a calibration solution vial containeruseful in the analyzer of FIG. 1;

FIG. 4 is a perspective view of an aliquot vessel array storage andhandling unit useful in the analyzer of FIG. 1;

FIG. 4A is a sampling probe useful in the analyzer of FIG. 1;

FIG. 4B is a wash station useful in the analyzer of FIG. 1;

FIG. 5 is an aliquot vessel array useful in the analyzer of FIG. 1;

FIG. 6 is a schematic plan view of a container transport system usefulin the analyzer of FIG. 1;

FIG. 7 is a perspective view of a container shuttle useful in theanalyzer of FIG. 1;

FIG. 8 is a perspective view of a container tray shuttle useful in theanalyzer of FIG. 1;

FIG. 9 is a viewing screen useful within the present invention;

FIG. 10 is a perspective view of an ion selective electrode measuringdevice useful within the present invention;

FIG. 11 is a perspective view of a photometric measuring device usefulwithin the present invention; and,

FIG. 12 is a perspective view of a LOCI measuring device useful withinthe present invention.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1, taken with FIG. 2, shows schematically the elements of anautomatic chemical analyzer 10 comprising a reaction carousel 12supporting an outer cuvette carousel 14 having cuvette ports 20 formedtherein and an inner cuvette carousel 16 having vessel ports 22 formedtherein, the outer cuvette carousel 14 and inner cuvette carousel 16being separated by a open groove 18. Cuvette ports 20 are adapted toreceive a plurality of reaction cuvettes 24 like disclosed in co-pendingapplication Ser. No. 09/949,132 assigned to the assignee of the presentinvention and containing various reagents and sample liquids forconventional clinical and immunoassay assays while vessel ports 22 areadapted to receive a plurality of reaction vessels 25 that containspecialized reagents for ultra-high sensitivity luminescentimmunoassays. Reaction carousel 12 is rotatable using stepwise cyclicmovements in a constant direction, the stepwise movements beingseparated by a constant dwell time during which carousel 12 ismaintained stationary and computer controlled assay operational devices13, such as sensors, reagent add stations, mixing stations and the like,operate as needed on an assay mixture contained within cuvettes 24 andreaction vessels 25.

Analyzer 10 is controlled by software executed by the computer 15 basedon computer programs written in a machine language like that used on theDimension® clinical chemistry analyzer sold by Dade Behring Inc, ofDeerfield, Ill., and widely used by those skilled in the art ofcomputer-based electromechanical control programming. Computer 15 alsoexecutes application software programs for performing assays conductedby various analyzing means within analyzer 10. The analyzer 10 accordingto the present invention includes multiple detection units 17A, 17B, 17Cand 17D, each including one or more detectors. In a preferredembodiment, each detection unit 17A, 17B, 17C and 17D, is adapted toperform different measurements and follow various analysis protocolsthat the other detection units. The diversity of detectors allowsmultiple types of tests to be run on the same system, thereby increasingthe likelihood that an analyte can be determined by an assay that ismost appropriate for that particular analyte, e.g, an assay that ishighly specific for the analyte, is accomplished in a reasonable periodof time, and is cost effective. The samples and reaction mixture may beanalyzed in the cuvettes 24, 25 while in their respective carousels 14,16, or may be moved into the detection units 17A, 17B, 17C and 17D, by aconventional cuvette transporter (not shown).

In the embodiment shown in FIG. 1, the analyzer 10 includes a detectionunit 17C exemplified by FIG. 12 which includes detector adapted todetect luminescence of a reaction mixture in one of the reaction vessels25. Preferably, the detector is a conventional luminometer 17C or achemiluminometer 17C. More preferably, the luminometer is configured asa LOCI reader 17C, that is, the luminometer preferably is configured toallow the analyzer 10 to perform luminescent oxygen channelingimmunoassays (“LOCI”). LOCI assays provide significant advantage overmany conventional immunoassays run on automated analyzers because LOCIis highly specific and can be performed without many of thetime-consuming separation steps typically associated with suchconventional immunoassays. Furthermore, LOCI is a reliable method andresults in less analyzer down time. As described previously, LOCI assaysinvolve measurement of luminescence from a chemiluminescent compoundwhich associates with a photosensitizer in the presence of a particularanalyte. Optimally, the chemiluminescent compound is photochemicallyactivated by singlet oxygen. The singlet oxygen is preferably producedby irradiating the photosensitizer. The light emitted by thechemiluminescent compound can be measured quantitatively to determinethe amount of analyte. Accordingly, the reagents stored in the storagearea 26 preferably include a photosensitizer and a complementarychemiluminescent compound. The detection unit 17C preferably issurrounded by an environmental chamber (shown in dotted lines) which isadapted to shield the detection unit 17C and the sample being analyzedfrom being exposed to environmental light, which would be detrimental tothe assay. Furthermore, the cuvettes 25 and/or the accompanying carousel16 may be configured to shield light sensitive reagents or reactionmixture from surrounding environmental light.

The remaining detection units 17A, 17B, 17D, may also be adapted todetect luminescence, however, they are preferably adapted to performdifferent, non-luminescence based analyses in order to optimize anddiversify the capabilities of the analyzer. For example, detection unit17A may include a photometer or a turbidometer. A suitable photometer isused as part of the Dimension® clinical chemistry analyzer manufacturedand sold by Dade Behring Inc. of Deerfield, Ill. Detection unit 17B mayinclude yet a different type of detector, such as a nephelometer.Furthermore, detection unit 17D preferably includes yet another,different type of detector, such as an ion selective electrode.

Computer 15 is interlinked using known interface software applicationswith a Laboratory Information System (LIS) and/or a Hospital InformationSystem (HIS) so that information concerning patients, patient assayrequests, assay results, analyzer status, and the like, may beimmediately accessible as needed by laboratory personnel. Computer 15includes an operator interface module typically comprising a keyboardand monitor or a flat-panel touch viewing screen or the like, on whichinformation about the operational status of analyzer 10 as describedherein may be called up and displayed or which may be automaticallydisplayed like in the instance of a malfunction within analyzer 10.

Temperature-controlled reagent storage areas 26, 27 and 28 store aplurality of multi-compartment elongate reagent containers 30 like thatillustrated in FIG. 3 and containing reagents necessary to perform agiven assay within a number of wells 32, each well containing as much as3.4 mL of a given reagent. Container 30 has features to enable analyzer10 to automatically determine whether a reagent container 30 is new andunused or whether the reagent container 30 has been previously used andpossibly become contaminated whenever a reagent container 30 isinitially placed onto an analyzer. FIG. 3A shows a calibration vialcontainer 30A containing calibration solutions of known analyteconcentrations in calibration solution vials 30V, the solutions being toconduct well-know calibration and quality control procedures withinanalyzer 10. Calibration vial containers 30A are also inventoried uponanalyzer 10 within reagent storage areas 26, 27 and 28

A bi-directional incoming and outgoing sample tube transport system 36having input lane 34A and output lane 34B transports incoming individualsample tubes 40 containing liquid specimens to be tested and mounted insample tube racks 42 into the sampling range of a liquid sampling probe44, like disclosed in co-pending application Ser. No. 10/623,311assigned to the assignee of the present invention. Liquid specimenscontained in sample tubes 40 are identified by reading bar coded indiciaplaced thereon using a conventional bar code reader to determine, amongother items, a patient's identity, tests to be performed, if a samplealiquot is to be retained within analyzer 10 and if so, for what periodof time. It is also common practice to place bar coded indicia on sampletube racks 42 and employ a large number of bar code readers installedthroughout analyzer 10 to ascertain, control and track the location ofsample tubes 40 and sample tube racks 42.

Sampling probe 44 comprises a translatable liquid sampling probe 48 sothat movement of sampling arm 44 describes an arc intersecting thesample tube transport system 36 and an aliquot vessel array transportsystem 50, as seen in FIG. 4. Sampling probe 44, as seen in FIG. 4A,comprises a Horizontal Drive 44H, a Vertical Drive 44V, a Wash Module44W, a Pump Module 44P and a Cleansing Module 44C having the primaryfunctions described in Table 1 below, so that sampling probe 44 isoperable to aspirate liquid sample from sample tubes 40 and to dispensean aliquot sample into one or more of a plurality of vessels 52V inaliquot vessel array 52, as seen in FIG. 5, depending on the quantity ofsample required to perform the requisite assays and to also provide fora sample aliquot to be retained by analyzer 10 within environmentalchamber 38.

TABLE 1 Module Primary Functions Horizontal 1. Position Vertical Drive44V over sample fluid tubes Drive 44H 40 on a rack 38, over individualvessels 52V of aliquot vessel arrays 52 and over Cleansing Module 44CVertical 1. Position a sampling probe 44P at vertical positions Drive44V for aspiration and dispense operations 2. Drive probe 44P throughthe stopper 44S of a sample fluid tube 40 3. Determine liquid level ofsample fluid in sample tube 40 4. Monitor aspiration quality Wash 1.Remove contamination from probe 44C with liquid Module 44W cleansingsolutions Cleansing 1. Cleansing interior and exterior surfaces ofsample Module 44C fluid probe 44P Pump Module 1. Aspirate and dispensesample fluid 44P 2. Wash probe 44P Wash 1. Connect Wash Module 44W andPump Module 44P Manifold 44M to probe 44P

Environmental chamber 38 is operated by computer 15 to ensure that thesame patient specimen is tested a second time following a previous firsttesting. For reasons of processing efficiency, it is sometimes desirableto automatically reprocess a sample aliquot that has been retained inwithin environmental chamber 38 for a predetermined period of time.Incoming samples to be tested may be identified by bar coded indiciaplaced on sample tubes 40 to determine if a sample aliquot is to beretained, and if so, for what period of time. In addition to a firstsample aliquot taken from a patient's specimen to be tested, a secondsample aliquot is also taken from the same patient's specimen and isretained in within environmental chamber 38. If it becomes desirable tore-test or additionally test a patient's sample some period of timeafter tests on the first sample aliquot are completed, reported, andanalyzed by a physician, the second sample aliquot may be quicklyremoved from within environmental chamber 38 and tested on analyzer 10,thereby saving time as well as providing for the exact same patientspecimen to be tested.

A conventional ion selective electron measuring station 17D equippedwith a conventional ion selective electron probe 49 may be convenientlylocated proximate aliquot vessel array transport system 50 in order toconduct ionic analyte measurements on sample aliquots aspirated fromvessels 52V by probe 49 and dispensed into the ion selective electronmeasuring station 17D, seen in FIG. 10.

Aliquot vessel array transport system 50 comprises an aliquot vesselarray storage and dispense module 56 and a number of linear drive motors58 adapted to bi-directionally translate aliquot vessel arrays 52 withina number of aliquot vessel array tracks 57 below a sample aspiration anddispense arm 54 located proximate reaction carousel 12. Sampleaspiration and dispense arm 54 is controlled by computer 15 and isadapted to aspirate a controlled amount of sample from individualvessels 52V positioned at a sampling location within a track 57 using aconventional liquid probe 54P and then liquid probe 54P is shuttled to adispensing location where an appropriate amount of aspirated sample isdispensed into one or more cuvettes 24 in cuvette ports 20 for testingby analyzer 10 for one or more analytes. After sample has been dispensedinto reaction cuvettes 24, conventional transfer means move aliquotvessel arrays 52 as required between aliquot vessel array transportsystem 50, environmental chamber 38 and a disposal area, not shown.

A number of reagent aspiration and dispense arms 60, 61 and 62 eachcomprising at least one conventional liquid reagent probe, 60P, 61P and62P, respectively, are independently mounted and translatable betweenreagent storage areas 26, 27 and 28, respectively. Probes 60P, 61P and62P are conventional mechanisms for aspirating reagents required toconduct specified assays at a reagenting location from wells 32 in anappropriate reagent container 30, the probes 60P, 61P and 62Psubsequently being shuttled to a reagent dispensing location wherereagent(s) are dispensed into reaction cuvettes 24. Probes 60P, 61P and62P are also used for aspirating calibration and control solutions fromcalibration solution vials 30V as required to conduct calibration andcontrol procedures necessary to ensure proper operation of analyzer 10,the probes 60P, 61P and 62P subsequently being shuttled to a calibrationsolution dispensing location where solutions(s) are dispensed intoreaction cuvettes 24 and analyzed by analyzing means 17.

Reaction cuvette load station 61 and reaction vessel load station 63 arerespectively positioned proximate outer cuvette carousel 14 and innervessel carousel 16 and are adapted to load reaction cuvettes 24 intocuvette ports 20 sideways as described later and reaction vessels 25into vessel ports 22 using for example a translatable robotic arm 65. Inoperation, used cuvettes 24 in which an assay has been finallyconducted, are washed and dried in a wash station 67 like disclosed inco-pending application Ser. No. 10/623,360 assigned to the assignee ofthe present invention. Computer 15 operates wash station 67 so that aused reaction cuvette 24 is cleansed so that whenever certain“exceptional” assays are scheduled to be next performed in a reactioncuvette 24, the used reaction cuvette 24 is automatically subjected toan additional cleansing or cleaning operation, the terms “cleaning andcleansing” including washing, rinsing, and drying. This selectivecleaning of a used reaction cuvette 24 is partially achieved byproviding a number of washing and drying manifolds 67M, like seen inFIG. 4B, each of which is independently selectively activated to performor not perform a cleansing operation, depending upon the identity of theassay scheduled to be next performed in that reaction cuvette 24.Further, wash station 67 is operated by computer 15 so that biohazardwaste residues from biochemical reactions in a cuvette 24 are segregatedfrom chemical waste residues from chemical reactions in a cuvette 24 andare safely disposed into secure biochemical waste storage 67B andchemical waste storage 67C by means of vacuum lines 67V.

Subsequent assays are conducted in cleaned used cuvettes 24 unlessdictated otherwise for reasons like disclosed in co-pending applicationSer. No. 10/318,804 assigned to the assignee of the present invention.Computer 15 is programmed to determine not to reuse a cleaned usedreaction cuvette 24 whenever an assay scheduled to be next performed ina cleaned used reaction cuvette 24 might be adversely affected by anycontaminants remaining from the assay previously performed in a cleanedused reaction cuvette 24. In addition, computer 15 may operate analyzer10 so that whenever certain assays are scheduled to be next performed ina cleaned used reaction cuvette 24, the cleaned used reaction cuvette 24is automatically removed, discarded, and replaced with a fresh, unusedreaction cuvette 24. Computer 15 may optionally control analyzer 10 sothat whenever an assay is scheduled to be next performed in a cleanedused reaction cuvette 24, and the same assay was previously performed inthe cleaned used reaction cuvette 24 and the assay results were outsidenormal test ranges, the cleaned used reaction cuvette 24 would beautomatically removed, discarded, and replaced with a fresh, unusedreaction cuvette 24. Cuvette unload station 59 is adapted to removeunusable reaction cuvettes 24 from cuvette ports 20 again using atranslatable robotic arm 65 like seen on load stations 61 and 63.

In order to re-supply assay reagents and calibration solutions as theyare exhausted by assay demand, analyzer 10 includes a single,bi-directional linear container shuttle 72 illustrated in FIG. 6 andadapted to remove reagent containers 30 and calibration vial containers30A from a container loading tray 29 having a motorized rake 73 thatautomatically locates containers 30 and 30A at a loading positionbeneath container shuttle 72. Shuttle 72 is further adapted to dispose areagent container 30 or a calibration vial container 30A into slots inat least one slotted reagent container tray 27T or 28T within reagentstorage areas 27 or 28, respectively. In a similar fashion, shuttle 72is even further adapted to remove reagent containers 30 or calibrationvial containers 30A from reagent container trays 27T and 28T and todispose such reagent containers 30 or calibration vial containers 30Ainto either of two concentric reagent carousels 26A and 26B withinreagent storage area 26. Shuttle 72 is also adapted to move reagentcontainers 30 and calibration vial containers 30A between the twoconcentric reagent carousels 26A and 26B.

As indicated by the double-headed arc-shaped arrows, reagent carousel26A may be rotated in both directions so as to place any particular oneof the reagent containers 30 or calibration vial containers 30A disposedthereon beneath reagent aspiration arm 60. Although reagent carousel 26Bmay also contain reagent containers 30 and calibration vial containers30A accessible by reagent aspiration arms 60 and 62, carousel 26B ispreferably designated only for storing excess inventory of reagentcontainers 30 and calibration vial containers 30A. Any one of thereagent containers 30 disposed in reagent container trays 27T and 28Tmay be located at a loading position beneath container shuttle 72 or ata reagent aspiration location beneath aspiration and dispensing arms 61and 62, respectively, by reagent container shuttles 27S and 28S withinreagent storage areas 27 and 28, respectively. Reagent aspiration arms60 and 62 are shown in dashed lines to indicate that they are positionedabove the surfaces of reagent containers 30 inventoried in carousel 26B,and reagent container trays 27T and 28T, respectively.

Reaction cuvettes 24 supported in outer cuvette carousel 14 are alsoboth shown in dashed lines to indicate that they are positioned abovethe surfaces of reagent containers 30. FIG. 6 also shows a reagentpreparation station 74 connected to reagent operation carousel 26B bymeans of a first reagent container transfer device 75. Reagentpreparation station 74 is adapted to perform a number of reagentpreparation operations like chemical additions, re-mixing, hydrating dryreagent powders and the like as may be required. In addition, amotorized belt shuttle 78 connected to reagent operation carousel 26B bymeans of a second reagent container transfer device 77, thereby enablingan exchange of reagent containers 30 between similarly equippedanalyzers. A container shuttle system like seen in FIG. 6, is describedin co-pending U.S. patent Ser. No. 10/623,310, assigned to the assigneeof the present invention.

Container shuttle seen in FIG. 7 is adapted to automatically compensatefor unknown changes in length of a drive belt 72B driven by motor 72M byan automated tensioner 72T, disclosed in co-pending application Ser. No.10/623,311 and assigned to the assignee of the present invention, andadapted to maintain a constant tension on the drive belt 72B regardlessof rapid changes in its driving direction so that reagent containers 30and calibration vial containers 30A attached thereto by clamps 72C maybe accurately positioned along the direction of drive belt 72B, asindicated by the double-ended arrow, and disposed at their intendedlocation beneath reagent container shuttle 72 or within storage areas26, 27 or 28 as drive belt 72B wears. Reagent container shuttles 27S and28S are similar in design to one another, and as seen in FIG. 8, includea reagent container tray 28T secured to one leg of a drive belt 28B sothat tray 28T is free to be driven to and from along the direction ofdrive belt 28B, as indicated by the double-ended arrow. Consequently,reagent containers 30 within slots in tray 28T may be automaticallypositioned at a pick-up location beneath container shuttle 72.

From the preceding description of analyzer 10, it is clear to oneskilled in the art that the capabilities of analyzer 10 under thecontrol of computer 15 include the ability to automatically to movereagent containers 30 and calibration vial containers 30A betweencontainer loading tray 29, reagent container trays 27T and 28T, andreagent carousels 26A and 26B. By means of shuttles 27S and 28S,analyzer 10 is further capable of moving reagent containers 30 andcalibration vial containers in reagent container trays 27T and 28T toappropriate aspiration locations by probes 61P and 62P, respectively,(or to a loading location beneath shuttle 72) so that in combinationwith the capability of reagent carousels 26A and 26B to place anyreagent container 30 or calibration vial container 30A beneath reagentaspiration arms 60P, 61P and 62P. Analyzer 10 thus includes an automatedrandom access reagent and calibration solution re-supply system with theflexibility to position a large number of different reagents andcalibration solutions at different aspiration locations.

A key factor in maintaining an optimum assay throughput within analyzer10 is the ability to timely re-supply reagent containers 30 into reagentstorage areas 26, 27 and 28 before the reagents contained therein becomeexhausted. Similarly important is the ability to timely re-supplycalibration and Quality Control solutions in vial containers 30A beforethe solutions contained therein become exhausted so that calibration andcontrol procedures may be conducted as required, whether this be basedon the basis of time between calibrations or number of assays performedsince an immediately previous calibration or number of assay resultsoutside normal ranges, or changes in the performance of the analyzer.This challenge may be met by timely equipping analyzer 10 withadditional requisite calibration and Quality Control solutions used incalibration and control procedures and called standard chemicalsolutions herein for convenience, before they become exhausted, therebymaintaining assay throughput of analyzer 10 uninterrupted.

In order to maintain continuity of assay throughput, computer 15 isprogrammed to track reagent and assay chemical solution consumptionalong with time, and date of consumption of all reagents consumed out ofeach reagent container 30 and assay chemical solutions consumed out ofeach vial container 30A on a per reagent container, per calibration vialcontainer, per Quality Control container, per assay, and per calibrationbasis, for specifically defined time periods. As disclosed in co-pendingapplication Ser. No. 10/622,435 and assigned to the assignee of thepresent invention, computer 15 is programmed to make an inventory demandanalysis for specifically defined time periods so as to determine futureassay inventory demands for the specifically defined time periods anddisplay to an operator on a display viewing screen 15S like illustratedin FIG. 9 a list of all of the reagent containers 30 andcalibration/Quality Control vial containers 30A that will be needed inthe future in a timely manner prior to the actual need of said reagentcontainer 30 and calibration/Quality Control vial containers 30A.

A very simplified illustration of the analysis made by computer 15 maybe found in Table 1, wherein an average assay demand is conducted onMonday, using the most recent historical Tuesday-specific assay demandfor the four previous Tuesdays, for Total CO2, Creatinine, and BUN is1255, 1140, and 1050, respectively. In view of the number of assays thatmay be conducted in single different reagent containers 30 containingthe reagents needed to perform Total CO2, Creatinine, and BUN assays,and considering the on-board inventory of the different reagentcontainers 30 as indicated, it is clear that one additional reagentcontainer 30 for Total CO2 is needed for Tuesday and that two additionalreagent containers 30 for Creatinine and BUN are needed for Tuesday.This information is displayed on display viewing screen 15S so that therequisite different reagent containers 30 may be timely supplied intotray 29 of analyzer and shuttled throughout analyzer 10 as required by acontainer transport system like seen in FIG. 6 in order to maintain acontinuous throughput within analyzer 10.

TABLE 2 Reagent Additional Reagent Assays Per Averaged ContainersContainers 30 Reagent Assay Assay 30 on Needed on Container 30 TypeDemand Analyzer 10 Analyzer 10 540 Total CO2 1255 2 1 450 Creatinine1140 1 2 480 BUN 1050 1 2

As known in the art, an analyzer like analyzer 10 is not limited to thethree assays in Table 1, and instead is typically adapted to perform asmany as 180-200 different assays, with the reagents required to performabout 50% of these “on-board assays” always on-board analyzer 10 instorage areas 26, 27 and 28. In an exemplary embodiment of analyzer 10,in order to improve assay throughput, the reagent containers 30containing reagents required to perform all “on-board assays” would beheld in storage area 26 while the reagent containers 30 containingreagents required to perform less frequently requested all “on-boardassays” might be divided between storage areas 27 and 28. When operatedin this manner, about 250-500 assays per hour may be scheduled bycomputer 15 using reagent containers 30 held in storage area 26, whileabout 500 assays per hour may be scheduled by computer 15 using reagentcontainers 30 held in each of storage areas 27 and 28, so that computer15 is scheduling between 1,250 to 1,500 assays per hour. These assaythroughput values do not include about 375 ionic analyte measurementsfor sodium, potassium and chloride additionally performed by ionselective electron measuring station 47 on about 125 different samplesper hour in aliquot vessel wells 52V.

Throughput values like those just described may be achieved becauseduring operation of analyzer 10 by computer 15, different incomingsamples 40 for which different assays are to be performed arepartitioned into a number of separate assay groups in accord with thelength of time required for the assay to be completed on reactioncarousel 14, disclosed in co-pending application Ser. No. 10/151,424(DCS-9128) and assigned to the assignee of the present invention.Judicious partitioning of assays by time, taken with carefully designeddwell times, number of reaction vessels 24, and location of assaydevices 13 enables a first medium time length assay and a second shortertime length assay to be completed in less than a single operationalcycle, thereby increasing the analyzer's 10 volume throughput ascompared to conventional analyzers in which a reaction mixture havingbeen analyzed may remain on a reaction carousel for an unproductive timeperiod of inactivity. In particular, during a single full operationalcycle of reaction carousel 14, medium length time assays are firstcompleted within a number of reaction vessels 24; as each medium lengthtime assay is completed, those reaction vessels 24 are removed fromreaction carousel 14 and are replaced by new or cleaned reaction vessels24 in which shorter length time assays are then completed. Longer lengthtime assays remain on reaction carousel 14 during a full operationalcycle.

Clearly, from the above descriptions of the multiple operationsconducted within analyzer 10 as controlled by computer 15, it isapparent that a complex problem to be resolved is how to display to aclinical laboratory operator or to an analyzer technician on a displayviewing screen 15S like illustrated in FIG. 9, that informationpertinent to a given situation, in a “user-friendly” manner.

The display viewing screen 15S of a display module is segmented so thata significant portion, and preferably, a majority of the viewing screen15S displays routine operational information that is used in routineoperation of analyzer 10. Typically at least 90% of the viewing screen15S displays routine operational information that is used in routineoperation of analyzer 10. Routine operational information includes, forexample, information about entering a sample order, checking on thestatus of a sample being analyzed, reading sample results, reading alist of the reagent containers 30 and calibration/Quality Control vialcontainers 30A needed to be loaded into tray 29 the next day, and thelike. In contrast, less than 10% of the display viewing screen 15Sdisplays non-routine or advanced operational information that is used ina detailed examination of information concerning the operation ofanalyzer 10. Advanced operational information includes, for example,information about which reagent container 30 lot is being used tocurrently perform each of the different assays analyzer 10 is equippedto perform, the expiration dates of each of the reagent lots, thecalibration status of each of the reagent lots, a relative comparison ofcalibration coefficients between a new and a previous calibration, whatare the existing calibration acceptance criteria, and the like.

FIG. 9 is a specific example of display viewing screen 15S in which theroutine operational information occupies the lower, greater than 90% ofscreen 15S, identified as 9R and this information is easily accessedusing only the tab rows 9B and 9C at the bottom of screen 15S and theBack/Forward buttons 9D. FIG. 9 illustrates how computer 15 isprogrammed to structure screen 15S on an operator specific basis so thata routine user cannot stumble into complexity that they are unable tohandle. This structuring has implications in documentation and trainingprograms, and also makes it much easier to train an operator toaccomplish the essential functions required to maintain continuousthroughput in analyzer 10, without needing to provide extensive overalloperational knowledge. In contrast, older systems have been structured“by function”, in which for example, all the complexity of calibration,is displayed in the same screen space. The routine operator was facedwith the same functions available to the highly qualified and trainedoperator but did not have the training to address those issues. Theroutine screens used by computer 15 do not require a routine operator toeven be aware of the complex, non-routine operational aspects ofmaintaining throughput of analyzer 10. If a problem arises, an alert isdisplayed, and the routine operator is taken where they need to go toresolve the issue, and the tools to accomplish it are close at hand. Theroutine screens display simple information and it is very difficult, ifnot impossible, to make an error, like destroy the store's inventory bypushing the wrong button. There is an advanced mode interface, which isavailable to highly trained and qualified technicians knowledgeable inthe all of the non-routine aspects of a clinical chemistry system.

From the above description of analyzer 10, computer 15 is required to beprogrammed to control, among other items:

-   -   analytical modules 17A, 17B, 17C, 17D;    -   determine whether a reagent container 30 is new and unused;    -   to conduct well-know calibration and quality control procedures        as needed;    -   incoming and outgoing sample tube transport system 36;    -   patient's identity, the tests to be performed, if a sample        aliquot is to be retained within analyzer 10;    -   control and track the location of sample tubes 40, sample tube        racks 42, and aliquot vessel arrays 52;    -   operation of sampling probe 44;    -   inventory and accessibility of sample aliquots within        environmental chamber 38;    -   ion selective electron probe 49 and ion selective electron        measuring station 17D;    -   aliquot vessel array transport system 50;    -   reagent aspiration and dispense arms 60, 61 and 62 including        liquid reagent probes 60P, 61P and 62P;    -   reaction cuvette load station 61 and reaction vessel load        station 63;    -   wash station 67;    -   linear container shuttle 72, reagent carousels 26A and 26B,        shuttles 275 and 28S, reagent container trays 27T and 28T;    -   tracking reagent and assay chemical solution consumption along        with time, and date of consumption of all reagents consumed out        of each reagent container 30 and assay chemical solutions        consumed out of each vial container 30A on a per reagent        container, per calibration vial container, per Quality Control        container, per assay, and per calibration basis, for        specifically defined time periods; and,    -   scheduling between 1,250 to 1,500 assays per hour.

The above capabilities make possible the operation of analyzer 10 havinga photometer analyzer or a turbidometer analyzer 17A and/or anephelometer analyzer 17B like seen in FIG. 11 and a conventionalluminometer analyzer or chemiluminometer analyzer 17C like seen in FIG.12 and an ion selective electrode measuring station 17D like seen inFIG. 17D, thereby allowing for various diagnostic assays to be performedon a single analyzing system having higher sensitivity as well as fasterprocessing speeds.

Those skilled in the art will readily appreciate that other conventionaldetectors may be selected for the detection units 17A, 17B, 17C and 17D,and that the relative positioning of the detection units 17A, 17B, 17Cand 17D may be altered without departing from the scope of theinvention. In the embodiment shown, the detection unit 17D utilized asan ion-selective electrode is positioned near the aliquot vessel array52 from which it samples via a probe 49. However, in alternateembodiments, the detection unit 17D may be placed at other locations onthe analyzer.

It should be readily understood by those persons skilled in the art thatthe present invention is susceptible of a broad utility and application.Many embodiments and adaptations of the present invention other thanthose herein described, as well as many variations, modifications andequivalent arrangements will be apparent from or reasonably suggested bythe present invention and the foregoing description thereof, withoutdeparting from the substance or scope of the present invention.

Accordingly, while the present invention has been described herein indetail in relation to specific embodiments, it is to be understood thatthis disclosure is only illustrative and exemplary of the presentinvention and is made merely for purposes of providing a full andenabling disclosure of the invention. The foregoing disclosure is notintended or to be construed to limit the present invention or otherwiseto exclude any such other embodiments, adaptations, variations,modifications and equivalent arrangements, the present invention beinglimited only by the claims appended hereto and the equivalents thereof.

1. An automated analyzer comprising: a rotatable reaction carouselsupporting an outer cuvette carousel having cuvette ports formed thereinand an inner cuvette carousel having vessel ports formed therein; areaction cuvette load station positioned proximate said reactioncarousel and containing a plurality of reaction cuvettes therein, saidcuvette load station having means for placing said reaction cuvettesinto said cuvette ports; a reaction vessel load station positionedproximate said reaction carousel and containing a plurality of reactionvessels therein, said vessel load station having means for placing saidreaction vessels into said vessel ports; a luminescent oxygen channelingimmunoassay reader surrounded by a light-shielding environmental chamberpositioned proximate said reaction carousel and having means fordetecting luminescence from a LOCI immunoassay reaction mixture in atleast one of said reaction vessels; a detector comprising a photometeror a turbidometer or a nephelometer positioned proximate said reactioncarousel and having means for performing analysis of a reaction mixturein at least one reaction cuvette; a control mechanism having means forcontrolling said first and second detectors and said rotatable reactioncarousel, and an inventory of calibration and Quality Control solutions,wherein said inner cuvette carousel comprises means for moving saidreaction vessels to said luminescent oxygen channeling immunoassayreader and said outer cuvette carousel comprises means for moving saidreaction cuvettes to said detector.
 2. The automated analyzer of claim1, wherein said LOCI immunoassay reaction mixture comprises a sensitizercapable of generating singlet oxygen upon absorbance of light.
 3. Theautomated analyzer of claim 2, wherein said LOCI immunoassay reactionmixture further comprises a chemiluminescer capable of emitting lightupon reaction with singlet oxygen.
 4. The analyzer of claim 1, whereinthe control mechanism is programmed to track reagent and assay chemicalsolution consumption and to make an inventory demand to determine futureassay inventory demands for a specifically defined time periods anddisplay a list of all of the reagents and calibration/Quality Controlsolutions that will be needed prior to the actual need of said reagentsand solutions.
 5. An automated analyzer comprising: a rotatable reactioncarousel supporting an outer cuvette carousel having cuvette portsformed therein and an inner cuvette carousel having vessel ports formedtherein; a reaction cuvette load station positioned proximate saidreaction carousel and containing a plurality of reaction cuvettestherein, said cuvette load station having means for placing saidreaction cuvettes into said cuvette ports; a reaction vessel loadstation positioned proximate said reaction carousel and containing aplurality of reaction vessels therein, said vessel load station havingmeans for placing said reaction vessels into said vessel ports; aluminescent oxygen channeling immunoassay reader surrounded by alight-shielding environmental chamber positioned proximate said reactioncarousel and having means for detecting luminescence from a LOCIimmunoassay reaction mixture in at least one of said reaction vessels; adetector comprising a photometer or a turbidometer or a nephelometerpositioned proximate said reaction carousel and having means forperforming analysis of a reaction mixture in at least one reactioncuvette; a control mechanism having means for controlling said first andsecond detectors and said rotatable reaction carousel, and a cuvettewashing station, wherein said inner cuvette carousel comprises means formoving said reaction vessels to said luminescent oxygen channelingimmunoassay reader and said outer cuvette carousel comprises means formoving said reaction cuvettes to said detector.
 6. The automatedanalyzer of claim 5, wherein said LOCI immunoassay reaction mixturecomprises a sensitizer capable of generating singlet oxygen uponabsorbance of light.
 7. The automated analyzer of claim 6, wherein saidLOCI immunoassay reaction mixture further comprises a chemiluminescercapable of emitting light upon reaction with singlet oxygen.
 8. Theanalyzer of claim 5, wherein the control mechanism is programmed to: (1)not to reuse a cleaned used cuvette whenever an assay scheduled to benext performed in a cleaned used cuvette might be adversely affected byany contaminants remaining from the assay previously performed in acleaned used cuvette; and, (2) to automatically remove, discard, andreplace a cleaned used cuvette with a fresh, unused reaction cuvettewhenever predefined assays are scheduled to be next performed in thecleaned used cuvette.